The present invention relates to methods for the formation of superporous hydrogels having improved physical and mechanical properties.
Superporous hydrogels (SPHs) are porous networks of hydrophilic and/or hydrophobic polymer chains. SPHs contain a multiplicity of pores with diameters in the micrometer to millimeter range, which enable them to absorb tens of times their weight of aqueous fluids in just a fraction of a minute in a manner that is independent of their size in the dehydrated state. SPH pores are interconnected in the hydrogel matrix such that absorbing fluid can move freely through the channels (capillaries). These interconnecting pores allow the SPHs to swell much faster than conventional hydrogels that have the same swelling capacity. U.S. Pat. No. 6,271,278 describes the preparation of various SPHs in detail SPHs are also described by Chen, et al., in J. Biomed. Mater. Res. 44:53-62, 1999.
SPHs are generally prepared based on hydrophilic monomers, including acrylic acid and its salts, acrylamide, the potassium salt of sulfopropyl acrylate, hydroxyethyl acrylate, and hydroxyethyl methacrylate. Generally, the hydrophilic or hydrophobic nature of the primary monomer can control the SPH's properties, including swelling (capacity and rate) and mechanical properties (elasticity, compressive strength, and resiliency). In the case of hydrophilic superporous hydrogels, the swelling is favored by the presence of either ions in the polymer backbone (e.g., ionic monomers) or hydrophilic functional groups in the polymer, such as, for example, hydroxyl, carboxyl, amide, and amino groups. These hydrogels can swell to a very large size in a very short period of time. In contrast to their superior swelling properties, these hydrogels frequently suffer from weak mechanical properties. Conversely, enhanced mechanical properties can be achieved with less hydrophilic superporous hydrogels at the expense of favorable swelling properties.
SPHs can be useful as drug delivery systems (DDSs; see Park et al. (Biodegradable Hydrogels for Drug Delivery, 1993, Technomic Pub. Co.; and in Hydrogels and Biodegradable Polymers for Bioapplications (ACS Symposium Series, 627), 1996, Eds., Ottenbrite, et al., American Chemical Society, or by Park, et al., in U.S. Pat. No. 6,271,278. SPHs used as DDSs have been employed to release pharmaceutical agents from specific locations in the body over specific periods of time. In particular, SPHs have been employed as gastric retention devices, which prolong the time an orally administered drug resides in the upper GI tract thereby improving drug absorbance. For the purpose of gastric retention, several qualities are important in SPHs. The SPH must be able to swell to a size sufficient to delay release of the SPH from the stomach via the pyloric sphincter. It is generally thought that for oral dosage forms to remain in the stomach in the fasted state, their dimensions must be 15 mm or larger. Further, fasted state gastric conditions are characterized by an environment of greatly increased mechanical and chemical stress. Accordingly, a suitable SPH must be strong enough to resist the acidic conditions in the stomach as well as the pressures that occur during stomach contractions, which can exhibit maximum pressures in the range of 100 to 130 cm H2O.
One potential design for a gastric retention system involves the incorporation of a SPH inside a capsule suitable for human ingestion. Upon entering the stomach of the patient, the capsule disintegrates and releases the SPH, whereupon the SPH swells to promote gastric retention. To be used in this way, SPHs must exhibit sufficient swelling and mechanical properties to promote gastric retention None of the SPHs known in the art exhibit all of these properties. Thus, there remains a need in the art for SPHs having both adequate swelling and high-strength mechanical properties for use in a very harsh environments, such as the gastric medium of the stomach.